Achieving precise control of cellular processes drives possibilities for next-generation therapeutic approaches. However, existing technologies for influencing cell behavior primarily rely on specific drug delivery, limiting their ability to mimic natural cellular communication processes. In this work, we developed glucose-powered gold-silica (Au-SiO2) nanorobots that induce cell migration by generating steady-state hydrogen peroxide (H2O2) as a biochemical signaling molecule to mimic natural cellular communication with high spatial resolution. These nanorobots leverage the unique 2-in-1 catalytic activity of gold nanoparticles for glucose oxidation and H2O2 decomposition, allowing for precise control over the generation of steady-state H2O2 concentration and enhanced diffusion powered by glucose within the cellular microenvironment. We further demonstrated that at low dosages of nanorobots, the steady-state H2O2 generation promotes cell migration and proliferation, while higher dosages of nanorobots slow down cell proliferation. The proposed design of this biocompatible nanorobot is intended to enable communication with the environment and provide a noninvasive, biochemical command system for regulating cellular behavior. Additionally, we show proof of principle of a method by which nanorobots can augment wound healing and similar regenerative therapies.

• Klíčová slova
• cell signaling, communication, enhanced diffusion, nanorobot, steady-state,
• MeSH
• glukosa chemie   metabolismus   MeSH
• kovové nanočástice * chemie   MeSH
• lidé MeSH
• mezibuněčná komunikace * účinky léků   MeSH
• myši MeSH
• oxid křemičitý chemie   MeSH
• peroxid vodíku metabolismus   chemie   MeSH
• pohyb buněk účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• regenerativní lékařství * MeSH
• zlato chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukosa MeSH
• oxid křemičitý MeSH
• peroxid vodíku MeSH
• zlato MeSH

Cells attaching to the extracellular matrix spontaneously acquire front-rear polarity. This self-organization process comprises spatial activation of polarity signaling networks and the establishment of a protruding cell front and a non-protruding cell rear. Cell polarization also involves the reorganization of cell mass, notably the nucleus that is positioned at the cell rear. It remains unclear, however, how these processes are regulated. Here, using coherence-controlled holographic microscopy (CCHM) for non-invasive live-cell quantitative phase imaging (QPI), we examined the role of the focal adhesion kinase (FAK) and its interacting partner Rack1 in dry mass distribution in spreading Rat2 fibroblasts. We found that FAK-depleted cells adopt an elongated, bipolar phenotype with a high central body mass that gradually decreases toward the ends of the elongated processes. Further characterization of spreading cells showed that FAK-depleted cells are incapable of forming a stable rear; rather, they form two distally positioned protruding regions. Continuous protrusions at opposite sides results in an elongated cell shape. In contrast, Rack1-depleted cells are round and large with the cell mass sharply dropping from the nuclear area towards the basal side. We propose that FAK and Rack1 act differently yet coordinately to establish front-rear polarity in spreading cells.

• Klíčová slova
• Rack1, cell adhesion, cell dry mass, cell spreading, coherence-controlled holographic microscopy, extracellular matrix, focal adhesion kinase, front–rear polarity, quantitative phase imaging,
• MeSH
• buněčná adheze genetika   fyziologie   MeSH
• buněčné linie MeSH
• fibroblasty cytologie   metabolismus   MeSH
• fokální adhezní tyrosinkinasy genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• mikroskopie fázově kontrastní MeSH
• pohyb buněk genetika   fyziologie   MeSH
• polarita buněk genetika   fyziologie   MeSH
• receptory pro aktivovanou kinasu C genetika   metabolismus   MeSH
• RNA interference MeSH
• tvar buňky genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fokální adhezní tyrosinkinasy MeSH
• RACK1 protein, rat MeSH Prohlížeč
• receptory pro aktivovanou kinasu C MeSH

Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity leads to the modification of cell mechanics, force development and adhesion strength, and determines cell shape, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify this Hippo effector as the key determinant of cell mechanics in response to ECM cues.

• MeSH
• buněčná diferenciace genetika   fyziologie   MeSH
• buněčná membrána metabolismus   MeSH
• buněčné linie MeSH
• buněčný převod mechanických signálů genetika   fyziologie   MeSH
• extracelulární matrix metabolismus   MeSH
• fokální adheze genetika   metabolismus   fyziologie   MeSH
• HEK293 buňky MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• mikrofilamenta metabolismus   MeSH
• nádorové buněčné linie MeSH
• pohyb buněk genetika   fyziologie   MeSH
• proteiny buněčného cyklu MeSH
• rhoA protein vázající GTP genetika   metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory genetika   metabolismus   MeSH
• tvar buňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• jaderné proteiny MeSH
• proteiny buněčného cyklu MeSH
• rhoA protein vázající GTP MeSH
• transkripční faktory MeSH
• YY1AP1 protein, human MeSH Prohlížeč

Apico-basal polarity is typical of cells present in differentiated epithelium while front-rear polarity develops in motile cells. In cancer development, the transition from epithelial to migratory polarity may be seen as the hallmark of cancer progression to an invasive and metastatic disease. Despite the morphological and functional dissimilarity, both epithelial and migratory polarity are controlled by a common set of polarity complexes Par, Scribble and Crumbs, phosphoinositides, and small Rho GTPases Rac, Rho and Cdc42. In epithelial tissues, their mutual interplay ensures apico-basal and planar cell polarity. Accordingly, altered functions of these polarity determinants lead to disrupted cell-cell adhesions, cytoskeleton rearrangements and overall loss of epithelial homeostasis. Polarity proteins are further engaged in diverse interactions that promote the establishment of front-rear polarity, and they help cancer cells to adopt different invasion modes. Invading cancer cells can employ either the collective, mesenchymal or amoeboid invasion modes or actively switch between them and gain intermediate phenotypes. Elucidation of the role of polarity proteins during these invasion modes and the associated transitions is a necessary step towards understanding the complex problem of metastasis. In this review we summarize the current knowledge of the role of cell polarity signaling in the plasticity of cancer cell invasiveness.

• Klíčová slova
• AMT, EMT, invasion, plasticity, polarity,
• MeSH
• invazivní růst nádoru patologie   MeSH
• lidé MeSH
• nádory patologie   MeSH
• polarita buněk fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T₁ relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe.

• Klíčová slova
• fluorescence lifetime correlation spectroscopy, fluorescence microscopy, high throughput microscopy, magnetic resonance imaging, melanoma brain metastasis, nanoprobe, theranostics, zeta potential,
• MeSH
• barvení a značení MeSH
• cytoplazma metabolismus   MeSH
• fluorescenční spektrometrie MeSH
• glykogen metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• kontrastní látky chemie   MeSH
• lidé MeSH
• lyzozomy metabolismus   MeSH
• magnetická rezonanční tomografie metody   MeSH
• melanom metabolismus   patologie   MeSH
• molekulární sondy * MeSH
• molekulární zobrazování metody   MeSH
• multimodální zobrazování * MeSH
• nádorové buněčné linie MeSH
• nanotechnologie * MeSH
• pohyb buněk MeSH
• viabilita buněk MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glykogen MeSH
• kontrastní látky MeSH
• molekulární sondy * MeSH

During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

• Publikační typ
• časopisecké články MeSH